The ACLT variant of the surgical instability model in rabbits is a reproducible and effective model of OA. The cartilage lesions in this model and their response to therapy can be graded according to an adapted histological and histochemical grading system, though also this system is to some extent subjective and, thus, neither objective nor entirely reproducible.

Objective. To determine whether oral glucosamine alleviates cartilage degradation in an animal model of osteoarthritis (OA).Methods. The effect of 8 weeks of daily oral glucosamine hydrochloride on degeneration of articular cartilage was evaluated in rabbits in which anterior cruciate ligament transection (ACLT) was performed to induce OA. Animals were treated with glucosamine (n ‫؍‬ 16) or a placebo (n ‫؍‬ 16) and necropsied at 11 weeks. Seven unoperated rabbits served as controls. The articular cartilage was evaluated macroscopically and histologically and analyzed for total type II collagen and glycosaminoglycan (GAG) content.Results. Histologic analysis revealed that loss of proteoglycan, based on Safranin O-fast green staining, was significantly reduced in the lateral tibial plateau cartilage of ACL-transected limbs in the glucosamine group compared with ACL-transected limbs in the placebo group, with a similar, but not significant, trend for the lateral femoral condylar cartilage. Likewise, macroscopic analysis of cartilage showed that the lateral tibial plateau alone had a significantly lower rate of disease in the glucosamine group, which was consistent with the results of the independent histologic assessment. However, no significant treatment effect was detected when composite histologic scores were analyzed. A significant reduction in GAG content was observed in the femoral condyles of placebo-treated ACL-transected joints, but not in the same region of glucosamine-treated ACLtransected joints, compared with their respective contralateral unoperated joints.Conclusion. Oral administration of glucosamine had a detectable, site-specific, partial disease-modifying effect in this model of OA. From a clinical perspective, the administration of glucosamine did not prevent fibrillation and/or erosions of the articular cartilage in all of the treated animals, and no effects were detected in the medial joint compartments.In addition to decreasing pain, an ideal therapeutic agent for osteoarthritis (OA) would also prevent or retard the progression of established OA by reducing or, preferably, reversing the underlying pathologic processes (structure modifying), resulting in the retention or restoration of more normal articular cartilage function. The most common pharmacologic therapeutic agents currently used for OA are primarily palliative and include acetaminophen, nonsteroidal antiinflammatory drugs, corticosteroids, and hyaluronic acid (1,2). None of these drugs for OA are disease modifying.Analyses of many randomized clinical trials of oral glucosamine in OA patients support the contention that glucosamine is a symptom-modifying agent in OA (3-5), while investigators in many other trials have

The data reveal corresponding, progressive degenerative changes in articular cartilage and subchondral bone, including striking focal resorptive lesions, in the third carpal bone of racehorses subjected to repetitive, high impact trauma.

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Matrix and ossification front changes were frequently observed and significantly associated with cartilage canals suggesting that they may be physiological changes associated with matrix remodelling and development. The collagen structure was variable through the growing epiphysis and a differential in biomechanical properties at focal sites may predispose them to injury.

An indigenous population of 450-500 beluga whales (Delphinapterus leucas) inhabiting the St. Lawrence Estuary has been exposed chronically for more than 50 years to a complex mixture of industrial pollutants including organochlorinated compounds (OC), polycyclic aromatic hydrocarbons (PAH) and heavy metals. From 1983 to 1990, we have necropsied 45 well preserved carcasses out of a total of 120 beluga whales reported dead over this period. Of these 45 animals, nine were affected by 10 malignant neoplasms. Fifteen animals (33%) were affected by pneumonia. Milk production was compromised in eight of 17 mature females (41%), by inflammatory changes (seven animals) and cancer (one animal) which affected the mammary glands. Opportunistic bacteria were found in pure culture, and/or in significant amounts in at least two organs in 20 belugas (44%). The concentrations of both total PCBs and highly chlorinated PCB congeners were much higher in St. Lawrence animals than in Arctic beluga whales. OC-induced immunosuppression has been repeatedly demonstrated in a wide variety of animal species. Therefore, it is probable that the immune functions of St. Lawrence beluga whales are impaired. Benzo[a]pyrene adducts were detected in 10 of the 11 St. Lawrence beluga whales of which tissues (six livers, 10/11 brains) were analyzed by a method based on HPLC. No such adducts were found in four Arctic animals. Since benzo[alpha]pyrene is one of the most potent chemical carcinogens known to man, these compounds might be responsible for some of the cancers observed in that population. Overall, our findings contrast vividly with those of others who found that cancers are exceedingly rare in free-ranging odontocete populations and that the major causes for mortalities in these populations are bacteria, parasites, and trauma.

BackgroundActinobacillus pleuropneumoniae is the etiological agent of porcine pleuropneumonia, a respiratory disease which causes great economic losses worldwide. Many virulence factors are involved in the pathogenesis, namely capsular polysaccharides, RTX toxins, LPS and many iron acquisition systems. In order to identify genes that are expressed in vivo during a natural infection, we undertook transcript profiling experiments with an A. pleuropneumoniae DNA microarray, after recovery of bacterial mRNAs from serotype 5b-infected porcine lungs. AppChip2 contains 2033 PCR amplicons based on the genomic sequence of App serotype 5b strain L20, representing more than 95% of ORFs greater than 160 bp in length.ResultsTranscriptional profiling of A. pleuropneumoniae recovered from the lung of a pig suffering from a natural infection or following growth of the bacterial isolate in BHI medium was performed. An RNA extraction protocol combining beadbeating and hot-acid-phenol was developed in order to maximize bacterial mRNA yields and quality following total RNA extraction from lung lesions. Nearly all A. pleuropneumoniae transcripts could be detected on our microarrays, and 150 genes were deemed differentially expressed in vivo during the acute phase of the infection. Our results indicate that, for example, gene apxIVA from an operon coding for RTX toxin ApxIV is highly up-regulated in vivo, and that two genes from the operon coding for type IV fimbriae (APL_0878 and APL_0879) were also up-regulated. These transcriptional profiling data, combined with previous comparative genomic hybridizations performed by our group, revealed that 66 out of the 72 up-regulated genes are conserved amongst all serotypes and that 3 of them code for products that are predicted outer membrane proteins (genes irp and APL_0959, predicted to code for a TonB-dependent receptor and a filamentous hemagglutinin/adhesin respectively) or lipoproteins (gene APL_0920). Only 4 of 72 up-regulated genes had previously been identified in controled experimental infections.ConclusionsThese genes that we have identified as up-regulated in vivo, conserved across serotypes and coding for potential outer membrane proteins represent potential candidates for the development of a cross-protective vaccine against porcine pleuropneumonia.

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